R2: Rasagiline Rescue in Alzheimer's Disease Clinical Trial

• Sponsor: The Cleveland Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT02359552
• Collaborator: (none)
• Enrollment: 50
• Locations: 3
• Arms: 2
• Actual Duration (Months): 44.2
• Patients Per Site: 16.7
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This is a Phase II, randomized, double blind, placebo controlled, parallel group, proof of concept three-site study, to evaluate the effect of Rasagiline in the regional brain metabolism on 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (FDG-PET).

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: Rasagiline; Drug: Placebo	Phase 2

Detailed Description

The study consists of two phases: a 24 week double blind placebo controlled treatment period and a 4 week follow up period. Patients will be randomized in a 1: 1 ratio at baseline to receive either Rasagiline or matching placebo

The study drug will be given as 0.5 mg dose once daily for the 4 weeks, then increases to 1 mg daily for the next 20 weeks. A total of 50 subjects will be enrolled: 25 will receive Rasagiline and 25 will receive matching placebo for the 24-week treatment period.

Primary objective is to determine if exposure to 1 mg of Rasagiline daily is associated with improved regional brain metabolism in the treatment group compared to the placebo group in Alzheimer's Disease patients

Study Design

• Study Type: Interventional
• Actual Enrollment: 50 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A 24-week, Three-site, Randomized, Double Blind, Placebo Controlled, Parallel Group, Proof-of-concept Study to Evaluate Rasagiline in the Regional Brain Metabolism on FDG PET in Patients With Mild to Moderate Alzheimer's Disease
• Actual Study Start Date: May 1, 2015
• Actual Primary Completion Date: Aug 29, 2018
• Actual Study Completion Date: Jan 4, 2019

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit).	Drug: Placebo
Active Comparator: Rasagiline Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit).	Drug: Rasagiline

Outcome Measures

Primary Outcome Measures

1. Change in Regional Glucose Metabolism Between Week 24 and Baseline as Measured by 18F-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography (FDG-PET). [24 weeks]

   The primary outcome measure is the change from baseline to week 24 in FDG-PET as measured by Standard Uptake Units Regional (SUVR) in several pre-specified brain regions including the medial temporal, lateral temporal, posterior cingulate - precuneus, inferior parietal, middle frontal, anterior cingulate, and striatum. The SUVR change was calculated by subtracting the value at 24 weeks from baseline values. Negative values indicate increased hypometabolism (i.e. worsening of cell function).

Secondary Outcome Measures

1. Change in ADAS-Cog 11 (Alzheimer's Disease Assessment Scale - Cognitive 11) Score [Mean change in scores from baseline to week 24]

   The ADAS-Cog 11 (Alzheimer's Disease Assessment Scale - Cognitive 11) is a psychometric instrument that evaluates memory, attention, reasoning, language, orientation, and praxis. A higher score indicates more impairment. Scores from the original portion of the test range from 0 (best) to 70 (worse). We used total ADAS-Cog 11 scores, which is a sum of individual subscales. We calculated the change by subtracting the ADAS Cog score at week 24 from baseline score. A positive change indicates cognitive worsening.

2. Change in MMSE (Mini Mental Status Examination) Score [Mean change in scores from baseline to week 24]

   Measure Description: The MMSE (Mini Mental Status Examination) is a brief, frequently used screening instrument for AD drug studies. The MMSE evaluates orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two overlapping pentagons. A lower score indicates more cognitive impairment. The highest score is 30, range is between 0 (severe impairment) and 30 (cognitively normal). We calculated the change in scores by subtracting week 24 score from baseline. A negative score indicates clinical worsening.

3. Change in ADCS-ADL (Alzheimer's Disease Cooperative Study-Activities of Daily Living) Score [Mean change in scores from baseline to week 24]

   Measure Description: The ADCS-ADL (Alzheimer's Disease Cooperative Study-Activities of Daily Living) is an activities-of-daily-living inventory developed by the ADCS to assess functional performance in participants with AD. Using a structured interview format, study partners are queried as to whether participants attempted each item in the inventory during the past 4 weeks and their level of performance. The ADCS-ADL provides a total score from 0-78, with a lower score indicating greater severity. We calculated change by subtracting scores on week 24 test from the baseline score. A negative score indicates worsening ability to complete ADLs.

4. Change in NPI (Neuropsychiatric Inventory) Score [Mean change in scores from baseline to week 24]

   Measure Description: The behavioral outcome measure for this trial is the NPI (Neuropsychiatric Inventory). The NPI evaluates both the frequency and severity of 10 neuropsychiatric disturbances. Frequency assessments range from 1 (occasionally, less than once per week) to 4 (very frequently, once or more per day or continuously) as well as severity (1=mild, 2=moderate, 3=severe). The overall score is calculated by summing the severity and frequency of the subscale measures. The range of scores is 0-40. A score of 0 indicates no behavioral impairment and a score of 40 indicates severe behavioral impairment. We calculated change by subtracting Week 24 scores from baseline scores. A positive change indicates behavioral worsening.

5. Change in Digit Span [Mean change in scores from baseline to week 24]

   Measure Description: The Digit Span consists of repetition of increasing long strings of digits presented at 1 per second as read by the examiner and repeated by the subject.The score is the maximum number of digits the patient can repeat until they fail twice in a row. The reverse digit span is identical to the forward digit span except that the patient repeats the presented digits in reverse order. The score is the maximum number of digits the patient can repeat in reverse order until they fail twice in a row. Each correct response is worth one point with a maximum total score of 28. A higher score is better. We calculated change by subtracting week 24 score from baseline score. A negative score indicates worse performance over the course of study.

6. Change in COWAT (Controlled Oral Word Association Test) Score [Mean change in scores from baseline to week 24]

   Measure Description: Study participants are instructed, "I want to see how many words you can say beginning with a certain letter in one minute." The study participant's responses are recorded on the worksheet. Study participants are then given an additional one minute for each of two different letters using similar instructions. The score is the total number of acceptable words for the three trials combined. A higher score represents better performance. Responses are then judged for their acceptability (example for the use of proper nouns, numbers, repetitions and stem word with a different ending). The score is the total number of acceptable words for the three trials combined. A higher score represents better performance. We calculated change by subtracting week 24 scores from baseline scores. A negative score indicates worse performance.

7. Change in QoL-AD (Quality of Life - Alzheimer's Disease) Score [This assessment will be performed at the Baseline and Week 24 visits.]

   Measure Description: The QoL-AD (Quality of Life - Alzheimer's Disease) is a commonly used 13 item QoL scale that assesses items specific to QoL in patients with cognitive impairment. It is administered to the research partner with answers for the patient. Points are assigned to each item as follows: poor = 1, fair = 2, good = 3, excellent = 4.The total score is the sum of all 13 items. The range of score is from 0-52. We calculated the change by subtracting the scores on week 24 score from baseline. A negative value indicates worsening quality of life.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males or females 50 to 90 of age inclusive.

• Diagnosis of probable AD (NINCDS-ADRDA criteria)

• Positive fluoro-deoxyglucose PET ([18F]-FDG PET) scan compatible with AD as determined by the ADM Diagnostics LLC (ADMdx) Criteria at screening

• Mini Mental Status Exam = 12 - 22 (inclusive)

• Must have a study partner who is able and willing to comply with all required study procedures.

• Have at least eight years of education and should have previously (in pre-AD condition) been capable of reading, writing, and communicating effectively with others in English.

• If receiving therapy with a cholinesterase inhibitor and/or memantine, the dose of these agents has been stable for at least 3 months prior to screening

Exclusion Criteria:

• Any non-AD neurological disease

• MRI findings indication of a non-AD diagnosis

• Screening laboratory studies that are 1.5 times above or below the highest and lowest range of normal for each test respectively

• History of melanoma; history of malignancy within the past five years with the exception of basal cell or squamous cell cancer, in-situ cervical cancer, or localized prostate cancer

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic Lou Ruvo Center for Brain Health	Las Vegas	Nevada	United States	89106
2	Cleveland Clinic Main Campus	Cleveland	Ohio	United States	44195
3	Cleveland Clinic Lakewood Hospital	Lakewood	Ohio	United States	44107

Sponsors and Collaborators

• The Cleveland Clinic

Investigators

• Principal Investigator: Jeffrey L Cummings, MD, ScD, The Cleveland Clinic

Study Documents (Full-Text)

• Study Protocol - Feb 17, 2017
• Statistical Analysis Plan - Sep 9, 2014

More Information

Publications

• Cummings JL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology. 1997 May;48(5 Suppl 6):S10-6. Review.
• Folstein MF, Folstein SE, McHugh PR. "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975 Nov;12(3):189-98.
• Galasko D, Bennett D, Sano M, Ernesto C, Thomas R, Grundman M, Ferris S. An inventory to assess activities of daily living for clinical trials in Alzheimer's disease. The Alzheimer's Disease Cooperative Study. Alzheimer Dis Assoc Disord. 1997;11 Suppl 2:S33-9.
• Rosen WG, Mohs RC, Davis KL. A new rating scale for Alzheimer's disease. Am J Psychiatry. 1984 Nov;141(11):1356-64.

• Responsible Party: The Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT02359552
• Other Study ID Numbers: 14-519
• First Posted: Feb 10, 2015
• Last Update Posted: Nov 10, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Alzheimer Disease; Rasagiline

Study Results

Participant Flow

Recruitment Details	Patients were recruited based on physician referral from three Cleveland Clinic sites between May 2015 and January 2018
Pre-assignment Detail	Of 96 screened participants, 50 met inclusion criteria and were enrolled and randomized to treatment.

Arm/Group Title	Placebo	Rasagiline
Arm/Group Description	Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Placebo	Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Rasagiline
Period Title: Overall Study
STARTED	25	25
COMPLETED	22	21
NOT COMPLETED	3	4

Baseline Characteristics

Arm/Group Title	Placebo	Rasagiline	Total
Arm/Group Description	Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Placebo	Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Rasagiline	Total of all reporting groups
Overall Participants	25	25	50
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73.44 (7.12)	74.72 (7.35)	74.08 (7.19)
Sex: Female, Male (Count of Participants)
Female	11 44%	14 56%	25 50%
Male	14 56%	11 44%	25 50%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	25 100%	25 100%	50 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 4%	1 2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 4%	0 0%	1 2%
White	24 96%	24 96%	48 96%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	25 100%	25 100%	50 100%
Alzheimer's Disease Assessment Scale - Cognitive 11 score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	27.96 (10.53)	23.2 (6)	25.58 (8.81)
Mini Mental Status Examination (MMSE) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	19.04 (4.61)	21.24 (3.54)	20.14 (4.21)
Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	58.2 (11.1)	61.88 (8.44)	60 (9.96)
Neuropsychiatric Inventory (NPI) score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	8.28 (8.97)	7.62 (7.61)	7.96 (8.25)
digit span (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	11.76 (3.23)	13.08 (2.75)	12.42 (3.04)
Controlled Oral Word Association Test (cowat) score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	21.16 (13.16)	26.72 (12.6)	23.94 (13.06)
Quality of Life - Alzheimer's Disease (QoL-AD) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	39.58 (5.24)	36.73 (5.35)	38.22 (5.43)

Outcome Measures

1. Primary Outcome

Title	Change in Regional Glucose Metabolism Between Week 24 and Baseline as Measured by 18F-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography (FDG-PET).
Description	The primary outcome measure is the change from baseline to week 24 in FDG-PET as measured by Standard Uptake Units Regional (SUVR) in several pre-specified brain regions including the medial temporal, lateral temporal, posterior cingulate - precuneus, inferior parietal, middle frontal, anterior cingulate, and striatum. The SUVR change was calculated by subtracting the value at 24 weeks from baseline values. Negative values indicate increased hypometabolism (i.e. worsening of cell function).
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Rasagiline
Arm/Group Description	Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Placebo	Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Rasagiline
Measure Participants	25	25
Middle Frontal	-0.032 (0.030)	-0.011 (0.030)
Anterior Cingulate	-0.020 (0.021)	-0.003 (0.026)
Superior Frontal	-0.016 (0.022)	-0.003 (0.018)
Striatum	-0.024 (0.029)	-0.002 (0.028)
Medial Temporal	-0.015 (0.034)	-0.010 (0.034)
Lateral Temporal	-0.020 (0.029)	-0.016 (0.024)
Post Cingulate - Precuneus	-0.017 (0.023)	-0.016 (0.018)
Inferior Parietal	-0.025 (0.029)	-0.018 (0.022)

2. Secondary Outcome

Title	Change in ADAS-Cog 11 (Alzheimer's Disease Assessment Scale - Cognitive 11) Score
Description	The ADAS-Cog 11 (Alzheimer's Disease Assessment Scale - Cognitive 11) is a psychometric instrument that evaluates memory, attention, reasoning, language, orientation, and praxis. A higher score indicates more impairment. Scores from the original portion of the test range from 0 (best) to 70 (worse). We used total ADAS-Cog 11 scores, which is a sum of individual subscales. We calculated the change by subtracting the ADAS Cog score at week 24 from baseline score. A positive change indicates cognitive worsening.
Time Frame	Mean change in scores from baseline to week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Rasagiline
Arm/Group Description	Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Placebo	Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Rasagiline
Measure Participants	25	25
Mean (Standard Deviation) [score on a scale]	2.76 (4.3)	1.81 (4.43)

3. Secondary Outcome

Title	Change in MMSE (Mini Mental Status Examination) Score
Description	Measure Description: The MMSE (Mini Mental Status Examination) is a brief, frequently used screening instrument for AD drug studies. The MMSE evaluates orientation, memory, attention, concentration, naming, repetition, comprehension, and ability to create a sentence and to copy two overlapping pentagons. A lower score indicates more cognitive impairment. The highest score is 30, range is between 0 (severe impairment) and 30 (cognitively normal). We calculated the change in scores by subtracting week 24 score from baseline. A negative score indicates clinical worsening.
Time Frame	Mean change in scores from baseline to week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Rasagiline
Arm/Group Description	Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Placebo	Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Rasagiline
Measure Participants	25	25
Mean (Standard Deviation) [score on a scale]	-1.14 (2.27)	-0.65 (2.48)

4. Secondary Outcome

Title	Change in ADCS-ADL (Alzheimer's Disease Cooperative Study-Activities of Daily Living) Score
Description	Measure Description: The ADCS-ADL (Alzheimer's Disease Cooperative Study-Activities of Daily Living) is an activities-of-daily-living inventory developed by the ADCS to assess functional performance in participants with AD. Using a structured interview format, study partners are queried as to whether participants attempted each item in the inventory during the past 4 weeks and their level of performance. The ADCS-ADL provides a total score from 0-78, with a lower score indicating greater severity. We calculated change by subtracting scores on week 24 test from the baseline score. A negative score indicates worsening ability to complete ADLs.
Time Frame	Mean change in scores from baseline to week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Rasagiline
Arm/Group Description	Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Placebo	Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Rasagiline
Measure Participants	25	25
Mean (Standard Deviation) [score on a scale]	-3.23 (6.71)	-3.75 (7.27)

5. Secondary Outcome

Title	Change in NPI (Neuropsychiatric Inventory) Score
Description	Measure Description: The behavioral outcome measure for this trial is the NPI (Neuropsychiatric Inventory). The NPI evaluates both the frequency and severity of 10 neuropsychiatric disturbances. Frequency assessments range from 1 (occasionally, less than once per week) to 4 (very frequently, once or more per day or continuously) as well as severity (1=mild, 2=moderate, 3=severe). The overall score is calculated by summing the severity and frequency of the subscale measures. The range of scores is 0-40. A score of 0 indicates no behavioral impairment and a score of 40 indicates severe behavioral impairment. We calculated change by subtracting Week 24 scores from baseline scores. A positive change indicates behavioral worsening.
Time Frame	Mean change in scores from baseline to week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Rasagiline
Arm/Group Description	Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Placebo	Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Rasagiline
Measure Participants	25	25
Mean (Standard Deviation) [score on a scale]	2 (7.18)	0.2 (6.79)

6. Secondary Outcome

Title	Change in Digit Span
Description	Measure Description: The Digit Span consists of repetition of increasing long strings of digits presented at 1 per second as read by the examiner and repeated by the subject.The score is the maximum number of digits the patient can repeat until they fail twice in a row. The reverse digit span is identical to the forward digit span except that the patient repeats the presented digits in reverse order. The score is the maximum number of digits the patient can repeat in reverse order until they fail twice in a row. Each correct response is worth one point with a maximum total score of 28. A higher score is better. We calculated change by subtracting week 24 score from baseline score. A negative score indicates worse performance over the course of study.
Time Frame	Mean change in scores from baseline to week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Rasagiline
Arm/Group Description	Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Placebo	Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Rasagiline
Measure Participants	25	25
Mean (Standard Deviation) [score on a scale]	-1.18 (1.92)	-0.29 (3.08)

7. Secondary Outcome

Title	Change in COWAT (Controlled Oral Word Association Test) Score
Description	Measure Description: Study participants are instructed, "I want to see how many words you can say beginning with a certain letter in one minute." The study participant's responses are recorded on the worksheet. Study participants are then given an additional one minute for each of two different letters using similar instructions. The score is the total number of acceptable words for the three trials combined. A higher score represents better performance. Responses are then judged for their acceptability (example for the use of proper nouns, numbers, repetitions and stem word with a different ending). The score is the total number of acceptable words for the three trials combined. A higher score represents better performance. We calculated change by subtracting week 24 scores from baseline scores. A negative score indicates worse performance.
Time Frame	Mean change in scores from baseline to week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Rasagiline
Arm/Group Description	Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Placebo	Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Rasagiline
Measure Participants	25	25
Mean (Standard Deviation) [score on a scale]	-1.09 (6.31)	0.62 (5.55)

8. Secondary Outcome

Title	Change in QoL-AD (Quality of Life - Alzheimer's Disease) Score
Description	Measure Description: The QoL-AD (Quality of Life - Alzheimer's Disease) is a commonly used 13 item QoL scale that assesses items specific to QoL in patients with cognitive impairment. It is administered to the research partner with answers for the patient. Points are assigned to each item as follows: poor = 1, fair = 2, good = 3, excellent = 4.The total score is the sum of all 13 items. The range of score is from 0-52. We calculated the change by subtracting the scores on week 24 score from baseline. A negative value indicates worsening quality of life.
Time Frame	This assessment will be performed at the Baseline and Week 24 visits.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Rasagiline
Arm/Group Description	Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Placebo	Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Rasagiline
Measure Participants	25	25
Mean (Standard Deviation) [score on a scale]	-1.95 (3.28)	1.11 (3.77)

Adverse Events

Time Frame	Adverse event data were collected following signing of consent to completion of study week 28 (from May 2016 to August 2018). At each point of contact the research coordinator and PI collected data regarding any new symptoms or laboratory changes.
Arm/Group Title	Placebo		Rasagiline
Arm/Group Description	Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Placebo		Subjects will be randomized in 1:1 ratio to receive Rasagiline or the matching placebo 24-week double blind treatment. Subjects will take one 0.5 mg Rasagiline tablet or the matching placebo once a day on Baseline (Day 1) through Week 4. The dose will be titrated up to one 1 mg tablet or the matching placebo once a day starting on Week 5 until the Week 28 (end of treatment visit). Rasagiline
All Cause Mortality
	Placebo		Rasagiline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/25 (0%)		0/25 (0%)
Serious Adverse Events
	Placebo		Rasagiline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/25 (16%)		1/25 (4%)
Cardiac disorders
atrial fibrillation	0/25 (0%)	0	1/25 (4%)	1
Injury, poisoning and procedural complications
fall	1/25 (4%)	1	0/25 (0%)	0
Nervous system disorders
stroke	1/25 (4%)	1	0/25 (0%)	0
Psychiatric disorders
confusion	1/25 (4%)	1	0/25 (0%)	0
delusions	1/25 (4%)	1	0/25 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		Rasagiline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/25 (60%)		16/25 (64%)
Endocrine disorders
Elevated Thyroid Stimulating Hormone	1/25 (4%)	1	2/25 (8%)	2
Injury, poisoning and procedural complications
Fall	1/25 (4%)	1	2/25 (8%)	2
Psychiatric disorders
Agitation	2/25 (8%)	2	0/25 (0%)	0
Confusion	2/25 (8%)	2	2/25 (8%)	2
Delusions	3/25 (12%)	3	3/25 (12%)	3
Insomnia	2/25 (8%)	2	0/25 (0%)	0
Renal and urinary disorders
Abnormal UA	1/25 (4%)	1	2/25 (8%)	2
Skin and subcutaneous tissue disorders
Rash/skin lesion	1/25 (4%)	1	2/25 (8%)	2
Vascular disorders
Elevated blood pressure	2/25 (8%)	2	3/25 (12%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.